How Lactoferrin Supports Immunity
07 May 2021
This is part 2 of our series that discusses the role of Lactoferrin in immunity.
Whilst our previous lactoferrin article debunked claims around lactoferrin’s ability to specifically treat or prevent COVID-19, lactoferrin didn’t get its reputation as an immunity ‘super-ingredient’ for no reason!
Although most of the existing evidence comes from lab studies, rather than the 'gold standard' - double placebo-controlled human clinicals - there are some indications that lactoferrin could actually support aspects of both adaptive and innate immunity.
But what aspects are these? And how does lactoferrin do this?
Read on to find out, as we share our understanding of the current research.
Lactoferrin as an Immunity 'Super-ingredient'
Lactoferrin has been reported to be active against some viruses, bacteria, and fungi1,2. It does this in a variety of ways – for example, by depriving the pathogen of essential nutrients such as iron, thereby affecting their growth and metabolism, or (in the case of bacteria) by directly affecting the bacterial membrane to compromise bacteria3.
A first line of defence for our immune system
In addition, lactoferrin is able to activate the immune system via cytokine-like signals, causing it to produce antibodies, and can also bind endotoxin, which helps to modulate the activity of the host immune response.
Lactoferrin has also been found to act as an anti-inflammatory agent3, it is believed that lactoferrin achieves this by competing with IL-8, a molecule involved in immune cell activation (specifically cells called neutrophils), for binding sites, explaining its anti-inflammatory effects1.
Additionally, lactoferrin can intensify natural killer cell activity to enhance immune defence.
The sum of its parts
Part of the lactoferrin structure, known as the N1-domain, has been identified as being the site of antimicrobial activity.1
The N1-domain contains several different peptides (small protein chains) which are responsible for this antimicrobial activity.
These peptides are released when lactoferrin is digested in the intestine.2 Lactoferrin and its peptides have also been shown to prevent bacteria from sticking to host cells, or stop aggregation of bacterial pathogens and biofilm development.3
-  Endotoxin: A component of the cell wall of some bacteria, which can induce inflammation and fever as part of an immune response.
-  Natural killer Cell: A type of immune cell (white blood cell) that checks if other cells are ‘normal’ and destroys cells that are abnormal i.e. infected, mutated or cancerous.
Competing with pathogens for receptor sites
Lactoferrin can bind to many receptors in the body, actively competing with pathogens for these receptors1. Lactoferrin also binds to heparan sulphate proteoglycan molecules (HSPGs) which can be found on various human cell surfaces. HSPGs can be used by viruses to anchor themselves to host cells.
Once bound to HSPGs, the virus pathogen, then rolls onto the host cell membrane and looks for specific receptors. Viruses and bacteria, can then enter the host cells via these receptors (e.g. the ACE-II receptor).
Lactoferrin can also bind to the HSPG molecule, thereby competing with the virus or bacteria, to prevent these pathogens from attaching to cells and trying to enter them via these receptors2.
A natural way to support the immune system
Laboratory studies show that lactoferrin can support the body’s fight against pathogens in several ways. This means there is potential for lactoferrin to aid the human immune system. However, as with any research, care needs to be taken when interpreting the data.
Firstly, we should not look at a single study in isolation, but instead seek to understand what the bulk of the research is collectively saying – a principle called ‘scientific consensus’.
Secondly, findings from one piece of research should not be extrapolated to contexts or populations outside of the ones specifically studied.
The implication of this, is that whilst lactoferrin certainly shows promise for supporting general immunity, more clinical proof is needed to determine if it can be considered a treatment or preventative measure against a specific disease or health concern.
Clinical research is a dynamic field, where new findings can change our understanding of how certain treatments work. A such, NZMP continues to monitor lactoferrin research with interest, and endeavours to bring these updates and our sound scientific interpretation of these results to our customers.
-  Orsi, N. (2004). The antimicrobial activity of lactoferrin: current status and perspectives. Biometals, 17(3), 189-196.
-  Rao, A. G. (1995). Antimicrobial peptides. Mol. Plant-Microbe Interact, 8(6), 13.
-  Ellison, R. 3., Giehl, T. J., & LaForce, F. M. (1988). Damage of the outer membrane of enteric gram-negative bacteria by lactoferrin and transferrin. Infection and immunity, 56(11), 2774-2781.
-  Siqueiros-Cendón, T., Arévalo-Gallegos, S., Iglesias-Figueroa, B. F., García-Montoya, I. A., Salazar-Martínez, J., & Rascón-Cruz, Q. (2014). Immunomodulatory effects of lactoferrin. Acta Pharmacologica Sinica, 35(5), 557-566.
-  Legrand, D. (2016). Overview of lactoferrin as a natural immune modulator. The Journal of pediatrics, 173, S10-S15.
-  Conneely, O. M. (2001). Antiinflammatory activities of lactoferrin. Journal of the American College of Nutrition, 20(sup5), 389S-395S.
-  Elass E, Masson M, Mazurier J, Legrand D. Lactoferrin inhibits the lipopolysaccharide-induced expression and proteoglycan-binding ability of interleukin-8 in human endothelial cells. Infect Immun. 2002;70:1860–6
-  Farnaud, S., & Evans, R. W. (2003). Lactoferrin—a multifunctional protein with antimicrobial properties. Molecular immunology, 40(7), 395-405.
-  Bellamy, W., Takase, M., Wakabayashi, H., Kawase, K., & Tomita, M. (1992). Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N‐terminal region of bovine lactoferrin. Journal of Applied Bacteriology, 73(6), 472-479.
-  Singh, P. K., Parsek, M. R., Greenberg, E. P., & Welsh, M. J. (2002). A component of innate immunity prevents bacterial biofilm development. Nature, 417(6888), 552-555.
-  Kell, D. B., Heyden, E. L., & Pretorius, E. (2020). The biology of lactoferrin, an iron-binding protein that can help defend against viruses and bacteria. Frontiers in immunology, 11, 1221.
-  Lang, J., Yang, N., Deng, J., Liu, K., Yang, P., Zhang, G., & Jiang, C. (2011). Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans. PloS one, 6(8), e23710.